Contractile cells of the kidney in primary glomerular disorders: an immunohistochemical study using an anti-alpha-smooth muscle actin monoclonal antibody

Mesangial cells of the renal glomerulus are thought to have contractile properties, resembling those of smooth muscle cells. Since actin synthesis in mesangial cells is increased in selected animal models of glomerulonephritis, we evaluated the expression of alpha-smooth muscle actin (ASMA), the principal actin isoform found in smooth muscle cells, in biopsy specimens from patients with primary glomerular disorders and in control tissues. Normal glomeruli and glomeruli in acute tubulointerstitial disorders showed few or no ASMA-positive cells in the glomeruli. In contrast, ASMA expression in mesangial cells was increased in minimal change disease, focal segmental glomerulosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, and immunoglobulin A nephropathy. In membranoproliferative glomerulonephritis and cryoglobulinemic glomerulonephritis both mesangial and capillary loop ASMA-positive cells were observed with a segmental distribution. In addition, ASMA-positive interstitial cells were seen in many biopsy specimens and often were increased in number in biopsy specimens showing early interstitial fibrosis and tubular atrophy. We conclude that ASMA synthesis in mesangial cells is upregulated in a variety of glomerular disorders, frequently associated with increased cell proliferation and mesangial matrix production. This phenotypic change may be an indicator of mesangial cell activation after injury and may have important pathophysiologic consequences.     

Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer

Our objective was to quantify the targeting of the monoclonal antibody (mAb) MX35 F(ab')2 to micrometastatic epithelial ovarian cancer. This mAb detects a Mr 95,000 glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. Six patients with minimal residual disease from an imaging trial were injected with 2 or 10 mg of 131I- and 125I-labeled mAb MX35 F(ab')2. Biopsied samples were removed at second-look laparotomy 1-5 days post-i.v. or -i.p. infusion of antibody. Serial cryostat sections were stained by indirect immunoperoxidase method for antigen distribution and exposed to storage phosphor screens for quantitative autoradiography. Coregistration of tumor histology, antigen expression, and radionuclide distribution demonstrated specific localization in micrometastatic tumor foci (50 micrometer to 1 mm) found within tissue stroma. The radiolabeled antibody uptake determined by well scintillation counts ranged between 5.2 and 223.5 x 10(-4) percentage of injected dose/g of tumor tissue for 131I. Specific localization of mAb in tumor was determined by tumor:normal tissue (fat) ratios ranging from 0.9:1 to 35.9:1 for 131I. The high resolution and linear response of the storage phosphor screen imager was used to estimate the radionuclide activity localized in each micrometastatic site. Quantitation of phosphor screen response revealed microCi/g values of 0.026-0.341 for normal tissue and 0.184-6.092 for tumor biopsies, evaluated 4 or 5 days post-antibody injection. The tumor:normal tissue (adjacent to tumor) ratios were between 1 and 4 times greater using the phosphor screen method than well counter measurements, but even larger variations of ratios up to 20:1 were observed between tumor cell foci and stromal cells within the same tissue section. This study has demonstrated that mAb MX35 F(ab')2 localizes to the micrometastatic ovarian carcinoma deposits within the peritoneal cavity. The dosimetry results suggest a therapeutic potential for this antibody in patients with minimal residual disease (<5 mm).     

Transcriptional analysis of Marek''s disease virus (MDV) genes in MDV-transformed lymphoblastoid cell lines without MDV-activated cells

Prevention of the occurrence of diabetes-specific vascular complications is the final aim of clinical islet transplantation. Pancreatic islets isolated from adult pigs may be a suitable tissue source to transplant a large number of type 1 diabetic patients. Acute cellular rejection may be finally overcome by clinically applicable protocols for tolerance induction. However, primary nonfunction of the graft, as regularly observed in the porcine islet-to-rat xenotransplantation model, may be an additional problem. In this paper, species-specific inflammatory and immunological mechanisms are discussed which prevent early porcine islet graft function in rats but not in mice.     

Hydrophilation of glass surfaces II Reaction of quaternary ammonium compounds with surface hydroxyl groups

The reaction mechanism for the adsorption of hexadecyltrimethylammonium bromide (HTAB) on silica was investigated. Although measurements of the effects of pH and concentration of HTAB tended to support a cation exchange mechanism, infra-red analysis suggested that the adsorption was associated with a charge-transfer type of reaction.     

Towards a vulnerability assessment of the UK and northern European coasts: the role of regional climate variability

Within the framework of a Tyndall Centre research project, sea level and wave changes around the UK and in the North Sea have been analysed. This paper integrates the results of this project. Many aspects of the contribution of the North Atlantic Oscillation (NAO) to sea level and wave height have been resolved. The NAO is a major forcing parameter for sea-level variability. Strong positive response to increasing NAO was observed in the shallow parts of the North Sea, while slightly negative response was found in the southwest part of the UK. The cause of the strong positive response is mainly the increased westerly winds. The NAO increase during the last decades has affected both the mean sea level and the extreme sea levels in the North Sea. The derived spatial distribution of the NAO-related variability of sea level allows the development of scenarios for future sea level and wave height in the region. Because the response of sea level to the NAO is found to be variable in time across all frequency bands, there is some inherent uncertainty in the use of the empirical relationships to develop scenarios of future sea level. Nevertheless, as it remains uncertain whether the multi-decadal NAO variability is related to climate change, the use of the empirical relationships in developing scenarios is justified. The resulting scenarios demonstrate: (i) that the use of regional estimates of sea level increase the projected range of sea-level change by 50% and (ii) that the contribution of the NAO to winter sea-level variability increases the range of uncertainty by a further 10-20cm. On the assumption that the general circulation models have some skill in simulating the future NAO change, then the NAO contribution to sea-level change around the UK is expected to be very small (<4cm) by 2080. Wave heights are also sensitive to the NAO changes, especially in the western coasts of the UK. Under the same scenarios for future NAO changes, the projected significant wave-height changes in the northeast Atlantic will exceed 0.4m. In addition, wave-direction changes of around 20 degrees per unit NAO index have been documented for one location. Such changes raise the possibility of consequential alteration of coastal erosion.     

Castration, circumcision, and anti-Semitism.

In this study, the authors look at whether circumcision is a relevant variable in anti-Semitism as measured in a contemporary male gentile population. The 52-item A-S scale described by Levinson and Sanford was administered to 381 students drawn from various psychology courses at Princeton and Rutgers Universities. The subjects (Ss) included in this study are 142 gentile male undergraduates selected from the larger population and divided into two matched groups of 71 each. No reliable differences in attitude were found between circumcised and uncircumcised subjects. These findings indicate the relative unimportance of circumcision as an isolated factor in anti-Semitism. The implications for the relationships involving circumcision, castration, and anti-Semitism are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of monoglyceride content,cooling rate and shear on the rheological properties of olive oil/monoglyceride gel networks

Functionality of conventional fat spreads can be achieved without hydrogenation by the formation of stable network structures upon cooling of mixtures of monoglycerides (MGs) and vegetable oils from the melt. Such mixtures are healthy substitutes for margarine and butter. The effects of MG content, cooling rate and shear on the temperature ramp, mechanical spectra and hardness of olive oil/MG gel networks were investigated. A minimum MG volume fraction was necessary for formation of a gelled network, but this concentration was less than that needed for a space‐filling network structure. Onset of gel network or structure formation was indicated by a sudden divergence in value of the elastic modulus G′. The temperature at onset of structure formation, T_o, final G′ value and network hardness all increased with increase in MG content. High cooling rates led to low final G′ values but harder networks, and vice versa. Maximum gel network development occurred when moderate shear (about 300 s^?1) was applied at incipient gelation. Copyright © 2004 Society of Chemical Industry     

Death at a discount: how the tobacco industry thwarted tobacco control policies in US military commissaries

Background

The US military is perhaps the only retailer consistently losing money on tobacco. Military stores (commissaries and exchanges) have long sold discount‐priced cigarettes, while the Department of Defense (DoD) pays directly for tobacco‐related healthcare costs of many current and former customers. Tobacco use also impairs short‐term troop readiness.

Objective

To examine the long struggle to raise commissary tobacco prices and the tobacco industry''s role in this policy effort.

Methods

Analysis of internal tobacco industry documents, searches of government and military websites and newspaper databases, and interviews with key informants identified in the documents.

Results

Efforts to raise commissary tobacco prices began in the mid‐1980s. Opposition quickly emerged. Some military officials viewed tobacco use as a “right” and low prices as a “benefit”. Others raised issues of authority, and some saw the change as threatening the stores. The tobacco industry successfully exploited complex relationships among the Congress, the DoD, commissaries, exchanges and private industry, obstructing change for over a decade. Leadership from the Secretary and Assistant Secretaries of Defense, presidential support and procedural manoeuvring finally resulted in a modest price increase in 1996, but even then, high‐level military officials were apparently threatened with retaliation from pro‐tobacco Congressmen.

Conclusions

The longstanding military tradition of cheap cigarettes persists because of the politics of the military sales system, the perception within the military of tobacco use as a right, and tobacco industry pressures. Against its own best interests, the US military still makes tobacco available to service members at prices below those in the civilian sector.The US military includes 1.4 million active duty personnel, stationed worldwide. Their smoking prevalence is higher (33.8% in 2002) than the US Department of Defense (DoD) goal of ⩽20%,¹ exceeding the civilian rate of 23.6%.² Smoking diminishes even short‐term troop health and readiness^3,4 and increases medical and training costs.^5,6 As an authoritarian, hierarchical institution, DoD should, theoretically, be able to establish and implement strong tobacco control policies. Nonetheless, DoD sells its personnel tobacco products virtually tax free. Military health personnel and some members of Congress have long sought to address this contradiction. This case study shows how for more than a decade, the tobacco industry worked to defeat policy changes by framing cheap cigarettes as a “benefit”, mobilising Congressional and military‐affiliated allies, and exploiting DoD ambivalence about tobacco.